Polymorphonuclear neutrophils (PMNs) metabolize arachidonic acid into prostaglandins and hydroxylated-fatty acids. Much data suggests that this metabolism is important in the aggregation and degranulation response of PMNs to chemotactic factors, A23187, and arachidonic acid: a metabolite(s) of arachidonic acid may mediate or, alternatively, stimulate the release of a hydrophobic substance which mediates these PMN responses. Metabolism of radiolabelled arachidonic acid in stimulated PMNs will be studied. Isolation and identification of arachidonate derivatives and the postulated mediator(s) will use silicic acid column chromatography, thin layer chromatography, high pressure liquid chromatography, and gas-liquid chromatography-mass spectroscopy. Bioactivities of arachidonic acid, its derivatives, and the mediator(s) will be studied in assays of PMN chemotaxis, degranulation, aggregation, foreign surface adherence, and generation of reactive oxygen species. These substances will also be studied in rabbits by measuring their ability to induce neutropenia, pulmonary capillary leukostasis, and histologic lung injury when infused intravenously. The studies, then, attempt to define the role of arachidonic acid in PMN pathophysiology, identify a mediator of cell function with potential proinflammatory and tissue-injuring activity, and indicate ways of pharmacologically blocking undesirable PMN responses through use of arachidonic acid antimetabolites.